It has been known that peptide fragments derived from native enzymes are capable of recombination by non-covalent interaction to regenerate enzymic activity. See for example Anfinsen and Scheraga, Adv. Prot. Chem. 29, 205(1975) and Zabin and Willarejo, Ann. Res. Biochem. 44, 295 (1975).
Singh et al, Endocrinology 94, 883 (1974) disclose the treatment of human growth hormone with human plasmin so as to produce a modified human growth hormone missing residues 135-140 from the large disulfide loop of the protein.
Blake and Li, Int. J. Peptide Protein Res. 11, 315 (1978) have described the synthesis of [Nle.sup.170, Ala.sup.165, 182, 189 ]-HGH-(145-191), [Nle.sup.170, Ala.sup.165,182,189 ]-HGH-(140-191), and [Lys.sup.135, 136, 138, Glu.sup.137, 139, Nle.sup.170, Ala.sup.165, 182, 189 ]-HGH-(135-191). The non-covalent complemenation of the first two named compounds with [Cys(Cam).sup.53 ]-HGH-(1-34) produce recombination HGH compositions having full biological and immunological activity is described by Li et al., Biochem. Biophys. Res. Com. 82(1 ), 217 (1978).
The non-covalent complementation of the prolactin (PRL) inactive fragments PRL-(1-53) and PRL-(54-199) yields a recombinant having a low but measurable biological activity and the full immunoreactivity as well as circular dichroism spectra of the native hormone. See Birk and Li, Proc. Natl. Acad. Sci. U.S.A. 75(5), 2155 (1978).